Spontaneous cancers in dogs and cats are an underused group of naturally occurring malignancies that share many features with human cancers such as osteosarcoma, prostate and breast cancers, non-Hodgkin's lymphoma, melanoma, soft tissue sarcoma, head and neck carcinoma, and virally induced lymphomas. Treatment of pet animals - primarily dogs - with naturally occurring cancer helps researchers better understand the biology of cancer and to improve the assessment of novel treatments for humans. The National Cancer Institute (NCI) Comparative Oncology Program has a collection of cancer tissue samples from dogs that span five different histologies (mast cell tumor, hemangiosarcoma, soft tissue sarcoma, pulmonary tumor, osteosarcoma, lymphoma, and melanoma) with anywhere from 100-500 patients (dogs) per histology. Each patient has tumor and normal tissue, serum, plasma, whole blood, and urine. All patients are enrolled while treatment-nave and have clinical outcome data. RNA-Seq experiments on selected canine tissue samples from these tumor classes has been completed. Using bioinformatics analysis of the RNA-Seq data the team developed diagnostic biomarker panels, drug combination therapies, and important genes specific to each tumor type. Experiments will be performed to validate the biomarker and drug combination hypotheses and to determine mutations and copy number variations associated with the genes relevant to each tumor type. Similar analyses are ongoing using publicly available human RNA-Seq data. Biomarkers, drug combinations, and important genes that are found to be consistent across both human and canine analyses will then have the highest chance of being successful in a potential clinical trial.